We are studying the role in aging of the enzyme, choline acetyltransferase (CAT). This enzyme catalyzes the synthesis of acetylcholine (ACh), a neurotransmitter which controls both the contraction of muscles and many functions of the central nervous system. Deficiencies in the metabolism of ACh have been implicated in diseases such as schizophrenia, and have been well documented in Alzheimer's disease. By examining the properties of CAT, we plan to define its role in cholinergic metabolism, and to use this to understand the deficiencies in disease states. During the last year, we have further studied the partially purified enzyme, and have begun to make monoclonal antibodies to it. In the coming year we propose to finish obtaining these antibodies, and to characterize their properties. We shall continue to purify the enzyme, using both conventional techniques and immunoabsorbents based upon the monoclonal antibodies. We shall also examine further the regulatory properties of the enzyme, paying particular attention to the role of certain small molecules. Finally, we shall continue to examine various strains of mice to find suitable animal models for the cholinergic deficiency observed in aged humans. In all cases, we shall use the information as a basis to compare the properties of CAT in samples of aged vs young adult brain from humans.